Experts question study's asthma drug safety claim

NEW YORK (Reuters Health) - An author of a new industry-funded study on the safety of a commonly prescribed type of inhaled asthma drug says the findings should be "reassuring" to patients who use them. However, two researchers who have published studies of their own on the medications disagree.

The medications involved are called long-acting beta agonists, and they include Serevent (salmeterol, GlaxoSmithKline) and Foradil (formoterol, Schering). These drugs are also sold in combination with inhaled corticosteroids, such as Advair (salmeterol plus fluticasone, GlaxoSmithKline) and Symbicort (formoterol plus budesonide, AstraZeneca). They are used in the treatment of asthma, emphysema and chronic bronchitis.

Several studies have linked long-acting beta agonists to an increased risk of severe asthma attacks, hospital admission for asthma, and even deaths. Data suggest that African Americans may be more highly affected, both by asthma and by use of long-acting beta agonists than are Whites.

In the current study, Dr. David M. Lang of the Cleveland Clinic Foundation in Ohio and fellow investigators looked at data on asthma hospitalizations in Philadelphia from 1995 to 1999 and prescription rates for long-acting beta agonists and other asthma drugs.

In 1997, expert guidelines were released that recommended adding long-acting beta agonists to low-dose inhaled corticosteroids for patients whose asthma wasn't adequately controlled with the steroids.

Lang and his team found that asthma hospitalization rates increased with short-acting beta agonist prescription rates, but fell with long-acting beta agonist prescription rates.

They also observed that African Americans were six times more likely to be hospitalized for treatment of asthma (45.7 vs 7.6 per 10,000 for Caucasians). The risk was greater if they had been using short-acting beta agonists. However, use of long-acting beta agonists appeared to be protective, with lower rates of hospitalization.

Based on the findings, the researchers conclude in the August Annals of Allergy, Asthma and Immunology that these findings do not support the argument that treatment with long-acting beta agonists is a major cause of increased illness with asthma.

In an interview, Lang told Reuters Health: "This study contributes to this area of controversy by providing additional evidence that should be viewed as reassuring."

Dr. Christopher Cates of the University of London, who has authored several scientific reviews on the safety and effectiveness of asthma drugs, disagrees.

"Nothing should be concluded about the safety of long-acting beta agonist in asthma from this study design," he told Reuters Health via email. The authors did not determine if the medications were prescribed for asthma or for other breathing problems, he said.

The drugs are likely harmful, agreed Dr. Shelley Salpeter of Stanford University in California. She pointed out that both long-acting and short-acting beta agonists can cause the user to develop tolerance to the drug, which leads to worse reactions to asthma triggers.

"The purpose of the study was clearly to reassure readers of the safety of long-acting beta agonists," Salpeter told Reuters Health via email.

"It is clear" from her 2006 analysis of clinical trials, as well as other studies published since then, that such drugs are associated with increases in asthma hospitalizations, life-threatening exacerbations, and even deaths from asthma, Salpeter continued.

The real debate, Salpeter and Cates say, is not whether or not long-acting beta agonists are risky. Instead, today's controversy revolves around whether their combination with inhaled corticosteroids eliminates their risk entirely. Recent information suggests that the combination is still more dangerous than corticosteroids alone.

GlaxoSmithKline funded the current study with an unrestricted grant. The report states that the company was not involved in designing the study, interpreting the data, or writing the manuscript.

Nevertheless, Salpeter argues, the findings clearly show the company's influence, while other evidence shows that people taking long-acting beta agonists "should definitely be concerned."

Late last year, she noted, a Food and Drug Administration advisory committee recommended that salmeterol and formoterol be banned for use in asthma.